EP0506658B1 - Composition et procede de traitement de symptomes douloureux inflammatoires ou allergiques - Google Patents
Composition et procede de traitement de symptomes douloureux inflammatoires ou allergiques Download PDFInfo
- Publication number
- EP0506658B1 EP0506658B1 EP90911873A EP90911873A EP0506658B1 EP 0506658 B1 EP0506658 B1 EP 0506658B1 EP 90911873 A EP90911873 A EP 90911873A EP 90911873 A EP90911873 A EP 90911873A EP 0506658 B1 EP0506658 B1 EP 0506658B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition
- vanillyl
- methyl
- cis
- nonenamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 42
- 230000001354 painful effect Effects 0.000 title claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 8
- 230000000172 allergic effect Effects 0.000 title claims abstract description 6
- 208000010668 atopic eczema Diseases 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title abstract description 11
- 230000002757 inflammatory effect Effects 0.000 title abstract description 5
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 claims description 68
- 229960002504 capsaicin Drugs 0.000 claims description 33
- 235000017663 capsaicin Nutrition 0.000 claims description 33
- 239000006071 cream Substances 0.000 claims description 15
- 238000009472 formulation Methods 0.000 claims description 14
- 239000007924 injection Substances 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 8
- 210000004400 mucous membrane Anatomy 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- 230000002411 adverse Effects 0.000 claims description 3
- 239000006193 liquid solution Substances 0.000 claims description 3
- 239000006194 liquid suspension Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 239000006210 lotion Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 230000000202 analgesic effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 208000002193 Pain Diseases 0.000 description 16
- 239000003981 vehicle Substances 0.000 description 10
- 108090000189 Neuropeptides Proteins 0.000 description 8
- 210000003491 skin Anatomy 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 5
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 4
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 102000003797 Neuropeptides Human genes 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000779 depleting effect Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 2
- 206010024769 Local reaction Diseases 0.000 description 2
- 241000722363 Piper Species 0.000 description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 238000013222 sprague-dawley male rat Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- 235000002566 Capsicum Nutrition 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 235000007862 Capsicum baccatum Nutrition 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000452734 Eudoraea Species 0.000 description 1
- 239000006002 Pepper Substances 0.000 description 1
- 235000016761 Piper aduncum Nutrition 0.000 description 1
- 235000017804 Piper guineense Nutrition 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- 101800003906 Substance P Proteins 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 210000004960 anterior grey column Anatomy 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036403 neuro physiology Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a compound derived from plants of the Solanacea family, commonly known as hot red peppers. Capsaicin has been utilized over the last two decades to study the neurophysiology and pharmacology of pain, as well as for the treatment of certain types of neuropathies and skin disorders. Such use is disclosed, for example, in U.S. Patent No. 4,486,450, issued December 4, 1984, and entitled “Method Of Treating Psoriatic Skin And Composition," and U.S. Patent No. 4,536,404, issued August 20, 1985, and entitled “Method And Composition For Treating Post-Herpetic Neuralgia;” both patents issued to the applicant herein.
- capsaicin While capsaicin is useful in treating painful neurological and other disorders, its utility has been limited by a troublesome adverse reaction which almost invariably accompanies its use. This reaction is a localized stinging and burning sensation, which can be quite severe, on application of capsaicin topically to skin or mucous membranes or on injection into tissues such as the dermis, the cerebrospinal canal or into blood vessels.
- capsaicin When capsaicin is extracted from the pepper plant, such extracts contain a number of other compounds similar in structure to capsaicin, but with different properties. A number of these compounds, known as capsinoids, have been evaluated for their ability to deplete neuropeptides. None of these capsinoids has been found to be as effective as capsaicin in depleting the neuropeptides, and all of those known to have any measurable neuropeptide depleting activity also cause an uncomfortable degree of burning and stinging.
- compositions of cis-8-methyl-N-vanillyl-6- nonenamide incorporated in topical formulations suitable for application to skin or mucous membranes, which compositions can produce in both man and animals pronounced analgesia without the pronounced irritant effects of capsaicin.
- the invention also includes compositions of cis-8-methyl-N-vanillyl-6-nonenamide incorporated into other medicinal formulations suitable for injection, oral ingestion, pulmonary inhalation, rectal administration or ophthalmic or nasal administration.
- cis-8-methyl-N-vanillyl-6-nonenamide is substantially more potent than capsaicin and will produce less local irritation in the form of burning, stinging or vasodilitation than capsaicin.
- the invention also includes methods of using the inventive compositions to treat painful, inflammatory, or allergic disorders.
- formulations are provided that incorporate cis-8-methyl-N-vanillyl-6-nonenamide into pharmaceutically acceptable vehicles suitable for use in man and animals.
- Such formulations include those for application to the skin, such as solutions, creams, ointments, gels, lotions, or pastes.
- Such formulation also include those for application to mucous membranes, including opthalmic and nasal solutions and suspensions, suppositories, and plasticized formulations suitable for oral and vaginal applications.
- Cis-8-methyl-N-vanillyl-6-nonenamide may also be formulated in sterile solutions or suspensions suitable for intradermal, subcutaneous, intramuscular, intravenous, or cerebrospinal injection.
- Formulations within the scope of the invention also include those suitable for oral administration such as capsules, tablets, or liquid solutions or suspensions.
- the cis-8-methyl-N-vanillyl-6-nonenamide may be present in amounts of about 0.1-100.0 mg, and preferably about 0.5 - 50.0 mg, per tablet, capsule, or 5 ml dose of liquid solution or suspension.
- Suitable pharmaceutical vehicles for the cis-8-methyl- N-vanillyl-6-nonenamide whether for topical application to skin or mucous membrane, injection, or oral administration, and methods of preparing such formulations as are within the scope of the invention, will be readily apparent to and understood by those skilled in the art.
- the instant invention also comprises the method of applying, instilling, injecting, ingesting, or inhaling medicinal formulations containing cis-8-methyl-N-vanillyl-6-nonenamide in order to treat a wide range of painful and/or inflammatory disorders of man and animals such as neuropathies, skin disorders, arthritis, allergic disorders, and inflammatory bowel disorders.
- compositions of the instant invention and the methods of their use will be more readily comprehended from the following examples.
- Cis-8-methyl-N-vanillyl-6-nonenamide was incorporated into a pharmacologically inert cream vehicle at a concentration of 0.025% and capsaicin was incorporated into the same cream vehicle at the identical concentration.
- the two creams were applied to 5 cm diameter patches on the forearms of 75 human volunteers under a randomized double-blind design. Each cream was applied 4 times over a 48 hour period and then the patients were examined. Stinging, burning and erythema were noted and rated for severity in each area. It was observed that while relatively frequent and severe local reactions were noted with capsaicin, the application of cis-8-methyl-N-vanillyl-6- nonenamide caused much less frequent, milder local reactions.
- Cis-8-methyl-N-vanillyl-6-nonenamide in a concentration of .075% was incorporated into the inert cream vehicle of Example 1 and applied four times daily to the chest of a patient with painful postherpetic neuralgia who had been unable to tolerate the burning produced by earlier applications of capsaicin.
- the patient experienced no burning or stinging on application of the cis-8-methyl-N-vanillyl-6-nonenamide cream and within 2 weeks noted marked reduction of his pain.
- vehicle cream containing 0.75% capsaicin and an identical vehicle cream containing 0.75% cis-8-methyl-N-vanillyl-6- nonenamide were applied to the right and left feet and legs respectively of a patient with symmetrical diabetic neuropathy. Both creams were applied three times daily for 4 weeks. At the end of this 4 week treatment period, the left leg which had been treated with the cis-8-methyl-N- vanillyl- 6-nonenamide cream was markedly less painful than prior to treatment, while the right leg which had been treated with capsaicin cream demonstrated moderate reduction in pain. The patient complained of slight stinging and burning for the first 5 days on application of capsaicin cream, but no stinging or burning at any time during application of the cis-8-methyl-N-vanillyl-6-nonenamide.
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Neurosurgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Claims (14)
- Composition comprenant une quantité pharmaceutiquement efficace de cis-8-méthyl-N-vanillyl-6-nonenamide et un véhicule pharmaceutiquement acceptable.
- Composition selon la revendication 1 dans laquelle ladite composition est adaptée pour une application sur la peau.
- Composition selon la revendication 2 dans laquelle ledit véhicule est compris dans le groupe consistant en une lotion, une solution , une pommade, un gel ou une pâte.
- Composition selon la revendication 1 dans laquelle ladite composition est adaptée pour une application sur les muqueuses.
- Composition selon la revendication 4 dans laquelle ledit véhicule est compris dans le groupe consistant en des solutions, des suspensions, des suppositoires et des formulations plastifiées.
- Composition selon la revendication 1 dans laquelle ladite composition est adaptée pour l'injection.
- Composition selon la revendication 1 dans laquelle ladite composition est adaptée pour une administration orale.
- Composition selon l'une des revendications 1 à 7 dans laquelle ladite cis-8-méthyl-N-vanillyl-6-nonenamide est présente dans une quantité comprise entre environ 0,001% et environ 1% en poids.
- Composition selon la revendication 8 dans laquelle ladite cis-8-méthyl-N-vanillyl-6-nonenamide est présente dans une quantité comprise entre environ 0,005% et environ 0,25% en poids.
- Composition selon la revendication 7 dans laquelle ledit véhicule est sous la forme de capsules, de comprimés, de solutions liquides ou de suspensions.
- Composition selon la revendication 10 dans laquelle la cis-8-méthyl-N-vanillyl-6-nonenamide est présente dans une quantité d'environ 0,5-50 mg par capsule, ou par tablette, ou d'environ 5 ml de liquide.
- Composition selon l'une des revendications 1 à 11 pour l'utilisation comme analgésique.
- Composition selon la revendication 12 comparable en efficacité à la capsaicine, mais qui présente significativement moins d'effets secondaires locaux normalement associés à la capsaicine.
- Utilisation de la composition selon l'une des revendications 1 à 11 dans la préparation d'un médicament pour l'utilisation dans le traitement de la douleur ou de l'allergie.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/452,476 US5063060A (en) | 1989-12-19 | 1989-12-19 | Compositions and method for treating painful, inflammatory or allergic disorders |
US452476 | 1989-12-19 | ||
PCT/US1990/003674 WO1991008738A1 (fr) | 1989-12-19 | 1990-06-28 | Composition et procede de traitement de symptomes douloureux inflammatoires ou allergiques |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0506658A1 EP0506658A1 (fr) | 1992-10-07 |
EP0506658A4 EP0506658A4 (en) | 1993-03-03 |
EP0506658B1 true EP0506658B1 (fr) | 1996-05-29 |
Family
ID=23796595
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP90911873A Expired - Lifetime EP0506658B1 (fr) | 1989-12-19 | 1990-06-28 | Composition et procede de traitement de symptomes douloureux inflammatoires ou allergiques |
Country Status (13)
Country | Link |
---|---|
US (1) | US5063060A (fr) |
EP (1) | EP0506658B1 (fr) |
JP (1) | JPH0780761B2 (fr) |
KR (1) | KR950015056B1 (fr) |
AT (1) | ATE138567T1 (fr) |
AU (1) | AU645023B2 (fr) |
CA (1) | CA2070685C (fr) |
DE (1) | DE69027220T2 (fr) |
DK (1) | DK0506658T3 (fr) |
ES (1) | ES2087160T3 (fr) |
IL (1) | IL95820A (fr) |
RU (1) | RU2095060C1 (fr) |
WO (1) | WO1991008738A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7244446B2 (en) * | 2003-10-16 | 2007-07-17 | Winston Laboratories, Inc. | Method for providing long-lasting pain diminishment through topical or intranasal administration of civamide |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0648113A4 (fr) * | 1992-04-23 | 1996-12-04 | Berlex Lab | Emulsion d'huile minerale solide bioadhesive. |
US6063381A (en) * | 1993-05-19 | 2000-05-16 | Staggs; Jeff J. | Therapeutic uses of pungent botanicals and their related compounds |
US6635659B1 (en) * | 1995-03-20 | 2003-10-21 | Arrie Kegler | Topical formulation for arthritic symptoms treatment |
US6239180B1 (en) | 1995-11-08 | 2001-05-29 | The Regents Of The University Of California | Transdermal therapeutic device and method with capsaicin and capsaicin analogs |
US6248788B1 (en) | 1996-11-06 | 2001-06-19 | The Regents Of The University Of California | Therapeutic method with capsaicin and capasicin analogs |
US5840762A (en) * | 1996-01-12 | 1998-11-24 | Genderm Corporation | Method for the treatment of cardiac arrhythmias and shortening of action potential duration |
DE19622271A1 (de) * | 1996-06-03 | 1997-12-04 | Basf Ag | Chirale Verbindungen |
GB9711962D0 (en) * | 1997-06-10 | 1997-08-06 | Reckitt & Colmann Prod Ltd | Therapeutically active compositions |
JP4677063B2 (ja) * | 1997-07-18 | 2011-04-27 | 帝國製薬株式会社 | オランダカラシエキス配合外用製剤 |
US6284797B1 (en) * | 1999-04-12 | 2001-09-04 | Donald A. Rhodes | Topical treatment of pain and to promote healing |
SI1587506T1 (sl) * | 2002-12-18 | 2009-04-30 | Algorx 101 Interchange Plaza S | Zdravljenje s kapsaicinom |
AU2003299691B2 (en) * | 2002-12-18 | 2008-06-05 | Algorx Pharmaceuticals, Inc. | Administration of capsaicinoids |
US20040146464A1 (en) * | 2003-01-23 | 2004-07-29 | Bernstein Joel E. | Compositions and method for daily tooth and gum care |
US20050085552A1 (en) * | 2003-10-16 | 2005-04-21 | Winston Laboratories, Inc. | Method for providing long-lasting pain relief through intrathecal administration of civamide |
JP4797986B2 (ja) * | 2004-06-15 | 2011-10-19 | 味の素株式会社 | カプシノイド含有トウガラシ乾燥物およびその乾燥方法 |
WO2007013690A1 (fr) * | 2005-07-28 | 2007-02-01 | Ajinomoto Co., Inc. | Procédé permettant la préparation pour une application locale et supplément répondant aux besoins du client |
US20090093446A1 (en) * | 2007-10-05 | 2009-04-09 | Winston Laboratories, Inc. | Method for alleviating keratoconjunctivitis sicca |
US20110014269A1 (en) * | 2009-07-14 | 2011-01-20 | Winston Laboratories, Inc. | Civamide patch for localized post-incisional neuropathic pain |
US20110200669A1 (en) * | 2010-02-15 | 2011-08-18 | Winston Laboratories, Inc. | Method and compositions of civamide to treat disease of the intestines |
US11166925B2 (en) | 2018-08-23 | 2021-11-09 | Elorac, Inc. | Method for alleviating keratoconjunctivitis sicca |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4460602A (en) * | 1981-06-30 | 1984-07-17 | The Procter & Gamble Company | Urea derivatives |
US4546112A (en) * | 1981-12-14 | 1985-10-08 | The Procter & Gamble Company | Method for preventing or reducing dipilatory irritation |
US4536404A (en) * | 1983-06-16 | 1985-08-20 | Dermatological Enterprises, Ltd. | Method and composition for treating post-herpetic neuralgia |
US4493848A (en) * | 1983-07-14 | 1985-01-15 | The Procter & Gamble Company | Compositions and methods useful for producing analgesia |
US4599342A (en) * | 1984-01-16 | 1986-07-08 | The Procter & Gamble Company | Pharmaceutical products providing enhanced analgesia |
US4681897A (en) * | 1984-01-16 | 1987-07-21 | The Procter & Gamble Company | Pharmaceutical products providing enhanced analgesia |
US4702916A (en) * | 1985-12-03 | 1987-10-27 | Warner-Lambert Company | Analgesic stick compositions |
-
1989
- 1989-12-19 US US07/452,476 patent/US5063060A/en not_active Expired - Lifetime
-
1990
- 1990-06-28 CA CA002070685A patent/CA2070685C/fr not_active Expired - Lifetime
- 1990-06-28 EP EP90911873A patent/EP0506658B1/fr not_active Expired - Lifetime
- 1990-06-28 KR KR1019920701410A patent/KR950015056B1/ko not_active IP Right Cessation
- 1990-06-28 RU SU905052768A patent/RU2095060C1/ru active
- 1990-06-28 DK DK90911873.9T patent/DK0506658T3/da active
- 1990-06-28 DE DE69027220T patent/DE69027220T2/de not_active Expired - Fee Related
- 1990-06-28 WO PCT/US1990/003674 patent/WO1991008738A1/fr active IP Right Grant
- 1990-06-28 JP JP2510990A patent/JPH0780761B2/ja not_active Expired - Fee Related
- 1990-06-28 AU AU60648/90A patent/AU645023B2/en not_active Ceased
- 1990-06-28 AT AT90911873T patent/ATE138567T1/de not_active IP Right Cessation
- 1990-06-28 ES ES90911873T patent/ES2087160T3/es not_active Expired - Lifetime
- 1990-09-27 IL IL9582090A patent/IL95820A/en not_active IP Right Cessation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7244446B2 (en) * | 2003-10-16 | 2007-07-17 | Winston Laboratories, Inc. | Method for providing long-lasting pain diminishment through topical or intranasal administration of civamide |
Also Published As
Publication number | Publication date |
---|---|
KR920703041A (ko) | 1992-12-17 |
JPH0780761B2 (ja) | 1995-08-30 |
DE69027220T2 (de) | 1997-01-02 |
DE69027220D1 (de) | 1996-07-04 |
EP0506658A1 (fr) | 1992-10-07 |
AU6064890A (en) | 1991-07-18 |
CA2070685A1 (fr) | 1991-06-20 |
US5063060A (en) | 1991-11-05 |
KR950015056B1 (ko) | 1995-12-21 |
AU645023B2 (en) | 1994-01-06 |
ES2087160T3 (es) | 1996-07-16 |
CA2070685C (fr) | 1994-11-01 |
JPH05504546A (ja) | 1993-07-15 |
DK0506658T3 (da) | 1996-06-24 |
IL95820A (en) | 1996-08-04 |
WO1991008738A1 (fr) | 1991-06-27 |
ATE138567T1 (de) | 1996-06-15 |
RU2095060C1 (ru) | 1997-11-10 |
EP0506658A4 (en) | 1993-03-03 |
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